To the Editor: The recent randomized study of bipolar depression by L. Trevor Young, M.D., Ph.D., et al. (1), documenting a superior antidepressant response after adding paroxetine rather than a second mood stabilizer to an existing mood stabilizer, addressed a critical and unresolved area of research in the treatment of bipolar disorder. Because studies such as this are scarce, clinical decisions about when to introduce antidepressants for the treatment of bipolar depression remain highly debated (2).

Little attention has been paid in the literature to the distinction between depression that arises spontaneously (i.e., after remission from a prior mania) and depression that arises soon after the resolution of a manic episode (i.e., biphasic). Biphasic episodes of mania followed by depression have been reported to occur in as many as 58% of bipolar disorder patients (3), although even expert clinicians fail to reach consensus on the optimal first-line treatment strategy for depression that occurs immediately after a manic episode (2). Because depression that occurs as part of a biphasic episode could reflect a more cyclical overall disease process than depression that arises spontaneously in the course of bipolar disorder, the utility (and safety) of antidepressants, rather than more aggressive anticycling agents, remains an open issue.

Although the size of the group studied by Dr. Young et al. (1) precluded a definitive subanalysis of spontaneous versus biphasic depression, their data may nonetheless help shed light on this topic by generating hypotheses. Their exclusion of patients with known rapid cycling furthermore makes theirs an ideal group to address this issue, as they are unconfounded by the idiosyncracies of rapid cycling and possible previous antidepressant-induced changes in cycle frequency. In light of other data suggesting that depression that follows manias may portend a more favorable response to lithium treatment than depression that precedes manias (4), it would be a valuable added dimension to their study to provide preliminary observations in this regard.